Field of the Disclosure
The disclosure is generally directed to methods and compositions for reducing blood cholesterol levels, and more particularly to dietary supplements for reducing blood cholesterol levels.
Brief Description of Related Technology
Coronary heart disease is the leading cause of death in the United States. Stroke is the third leading cause of death. These two manifestations of cardiovascular disease cause nearly 40 percent of all deaths in the United States (Anderson et al., “National Vital Statistics Reports, Deaths: Leading Causes for 2002,” CDC, 53(17):1-92 (2005)).
Cardiovascular disease is caused by atherosclerosis in the blood vessels and arteries that supply the heart. Atherosclerosis is a process involving the gradual buildup of plaques (typically, over decades) on the inner linings of blood vessels and arteries. Over time, the plaques can occlude the blood vessels and arteries, causing ischemia (injury caused by insufficient blood flow and reduced oxygen to tissues) and/or infarction (cell death caused by ischemia). Plaques can also become unstable, rupture, and promote a thrombus (blood clot) that occludes a coronary artery. A severe plaque rupture in the coronary vasculature can lead to myocardial infarction (or heart attack).
Stroke is caused when pieces of plaque travel through the bloodstream and occlude an artery in the brain. Stroke can occur suddenly with immediate maximum neurologic deficit (loss of brain function).
Elevated blood cholesterol levels (total and LDL cholesterol levels) are considered risk factors for cardiovascular disease. In adults, total cholesterol levels of 240 mg/dL or higher are considered high risk, and levels from 200 to 239 mg/dL are considered borderline-high risk. About 99,900,000 of American adults have total cholesterol levels above 200 mg/dl, and about 34,500,000 have total cholesterol levels of 240 mg/dl or more (American Heart Association, Learn and Live, “High Blood Cholesterol and Other Lipids—Statistics” (2004)).
Other risk factors for cardiovascular disease include high blood pressure (140/90 mm Hg or higher), tobacco use, diabetes mellitus, overweight (body mass index of 25.0 to less than 30.0) and obesity (BMI of 30.0 or greater), physical inactivity (guidelines suggest at least 30 minutes of moderate exercise five times per week or at least 20 minutes of vigorous exercise three times per week), gender (males are at greater risk of developing cardiovascular disease), increasing age (55 years and older for men and 65 years or older for women), family history of early heart disease (having a mother or sister who has been diagnosed with heart disease before age 65, or a father or brother diagnosed before age 55) or family history of stroke. When one or more risks factors are identified in an individual, the risk of heart attack or stroke typically increases significantly.
Phytosterols are lipids having chemical structures similar to cholesterol, which are present in all plants including but not limited to vegetables, fruits, and grains, particularly in nuts, seeds, and plant oils. Phytosterols inhibit intestinal cholesterol absorption, thereby lowering plasma total and low-density lipoprotein (LDL) cholesterol levels. Daily consumption of about one to two grams of phytosterols reduces the risk for cardiovascular disease by about 25 to about 28% without causing any adverse effects. Twice per day consumption of about 0.40 grams of phytosterols or about 0.65 grams of phytosterol esters has also been shown to lower total cholesterol levels and LDL cholesterol levels by up to 10%.
Soluble fiber is found in certain foods including oats, peas, beans, certain fruits, and psyllium. Soluble fiber has been scientifically proven to reduce blood cholesterol levels, which may help reduce the risk of coronary vascular disease. Consumption of 10.2 grams psyllium per day over an eight week period lowered serum total cholesterol by 4% (p<0.0001) and LDL cholesterol by 7% (p<0.0001) relative to placebo in subjects already consuming a low-fat diet, with no effect on serum HDL or triacylglycerol concentrations. Similarly, consumption of 15 grams of beta-glucan daily over a three week period by individuals having initial total cholesterol levels exceeding 260 mg/dL reduced total cholesterol by about 19% and LDL cholesterol by about 23%. In another study, individuals having total cholesterol levels ranging from 210 to 326 mg/dL consumed 3.5 g of beta-glucan daily and experienced a 5.4% reduction, in total cholesterol after two weeks.
Guggul lipid has been long used to treat obesity and other weight related problems, and offers considerable benefits in preventing and treating atherosclerotic vascular disease. The effects of the administration of 50 mg of guggul lipid or placebo capsules twice daily for 24 weeks were compared as adjuncts to a fruit- and vegetable-enriched diet in the management of 61 patients with high cholesterol levels (31 patients were in the guggul lipid group and 30 were in the placebo group) in a randomized, double-blind fashion. Guggul lipid decreased the total cholesterol level by 11.7%, the low density lipoprotein cholesterol (LDL) by 12.5%, triglycerides by 12.0%, and the total cholesterol/high density lipoprotein (HDL) cholesterol ratio by 11.1% from the post-diet levels, whereas the levels were unchanged in the placebo group. The lipid peroxides, indicating oxidative stress, declined 33.3% in the guggul lipid group without any decrease in the placebo group. The combined effect of diet and guggul lipid at 36 weeks was as great as the reported lipid-lowering effect of many modern drugs. Guggul lipid contains ketonic steroid compounds known as guggulsterones, which have been shown to provide the lipid-lowering actions.
Policosanol is a mixture of long-chain primary aliphatic alcohols derived from the waxes of plants such as sugar cane (Saccharum officinarium) and yarns (e.g., Dioscorea opposita). Such long-chain primary aliphatic alcohols are also found in beeswax. There are a number of studies suggesting that policosanol consumption can lower cholesterol, inhibit experimentally induced atherosclerotic lesions of cerebral ischemia, help prevent the peroxidation of lipoproteins, and inhibit platelet aggregation. In one study, patients with LDL-cholesterol levels exceeding 160 mg/dl were randomized in double-blind fashion to receive policosanol (10 mg/day), lovastatin (20 mg/day), or simvastatin (10 mg/day). After eight weeks, policosanol reduced LDL-cholesterol levels by about 24%, lovastatin reduced LDL-cholesterol levels by about 22%, and simvastatin reduced LDL-cholesterol levels by about 15%. Additionally, HDL-cholesterol levels increased significantly in the policosanol group but not in the groups receiving statin drugs.
Dietary supplementation with salts of glucaric acid such as D-glucarate reduced serum cholesterol in rats (Walaszek et al., Nutr. Res., 16: 673-681 (1996)). Both calcium and potassium salts of D-glucarate were effective in lowering total cholesterol levels by about 13-15% and LDL cholesterol levels by about 30-35%. Notably, potassium hydrogen D-glucarate was effective in lowering both VLDL cholesterol and total triglycerides, but calcium D-glucarate did not demonstrate similar effects.
Anthocyanins are pigment compounds found in all plants, which have antioxidant and anti-inflammatory properties. Anthocyanins are generally considered to be flavonoids, and more specifically to be derivatives of 2-phenylo-benzo-g pyren. Hypertension, atherosclerosis, and diabetes can reduce the flexibility of arterial walls, which can contribute to poor blood flow and plaque formation. Rat aortas exposed to anthocyanin-enriched blueberry extract in vitro exhibited relaxation (Zaragoza et al., Arch. Farmacol. Toxicol., 11:183-188 (1985)). Other studies suggest that anthocyanins provide cardio-protective benefits including reducing platelet aggregation.
Coenzyme Q10 (CoQ10) is essential for human life. It catalyzes the formation and utilization of energy in every human cell. Some people do not manufacture enough CoQ 10, especially as they grow older. Research has shown that COQ10 deficiency is a major cause of cardiomyopathy, and congestive heart failure, and that these diseases can often be cured by CoQ 10 supplementation. Coenzyme Q 10 is commonly added to multivitamin preparations.
Phytoestrogens such as resveratrol have also been shown to have cardioprotective effects. Resveratrol is a polyphenolic compound found in the skin of red grapes, which is a powerful phytoestrogen, cardioprotectant, and anti-oxidant. Other sources of resveratrol include peanuts, mulberries, and the dried roots and stems of Polygonum cuspidatum. Resveratrol has been shown to induce leukotriene production in human neutrophils. Leukotrienes are powerful mediators of inflammatory reactions and are thought to be involved in the cellular processes that contribute to atherosclerosis (Pace-Asciak et al., Clin. Chim. Acta., 235:207-219 (1995)). Administration of resveratrol to rats which were fed a high cholesterol diet inhibited cholesterol and triglyceride liver deposition, lowered serum triglyceride and low-density lipoprotein (LDL) cholesterol levels, and reduced the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol (Arichi et al., Chem. Pharm. Bull., 30:1766-1770 (1982)).
Chromium helps to prevent the buildup of plaque in arteries by lowering harmful low-density lipoprotein (LDL) cholesterol and increasing beneficial high-density lipoprotein (HDL) cholesterol. Despite its benefits, chromium is difficult for the body to absorb and retain. Compounding the problem, the average American diet is low in chromium.
Pantethine is the disulfide dimer of pantetheine, the 4′-phosphate derivative of which is an intermediate in the conversion of the B vitamin pantothenic acid to coenzyme A. Large amounts of pantethine have been found to have lipid-lowering effects. Pantethine has been found to decrease serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL), and triglycerides.
Consumption of artichoke leaf extract (ALE) has also been shown to lower cholesterol levels. Also, the Chinese herb, Salvia miltiorrhiza (also known as dansheng), has been traditionally associated and recommended for heart conditions.
The progression of atherosclerosis and the onset of cardiovascular disease can be slowed or even prevented by reducing total and LDL cholesterol levels. Existing pharmaceuticals are capable of treating elevated cholesterol levels, but the majority cause significant side-effects, such as liver problems. Thus, a dietary supplement capable of reducing blood cholesterol levels without causing significant side-effects would represent a significant advance for treatment of cardiovascular disease.